Aminoglycosides remain clinically valuable against Staphylococcus aureus. Aminoglycoside resistance in S. aureus represents a critical One Health concern and is primarily driven by aminoglycoside-modifying enzymes (AMEs), which are frequently plasmid-encoded. Although regional studies have provided valuable insights, the global epidemiology of aminoglycoside resistance determinants remains poorly characterized because comprehensive data integrating human, animal, and environmental reservoirs are still lacking. This study addresses this gap by analyzing over 110,000 S. aureus genomes (2000–2025) to map the global resistome, quantify temporal and host-specific trends, and assess the association between genetic determinants and phenotypic resistance. We performed a retrospective One Health meta-analysis of 110,309 S. aureus genomes collected between 2000 and 2025 from 128 countries. Genomes were quality-filtered and aminoglycoside resistance determinants were identified using NCBI AMRFinderPlus (v4.0.23). Multilocus sequence typing and host-source harmonization (Human, Animal, Environment, Unknown) enabled clonal and reservoir stratification. Temporal trends in gene prevalence and resistance burden were modeled with robust regression. Geographic and host-associated structuring of key genes was assessed via χ2 and enrichment tests. Machine-learning models (elastic-net, random forests, XGBoost) were benchmarked for minimum inhibitory concentration (MIC) prediction via nested cross-validation, with performance evaluated by mean absolute error, RMSE, and SHAP-based feature importance. All analyses were conducted in R and Python using publicly available, de-identified genomic data. Aminoglycoside resistance-associated genes were dominated by modifying enzyme determinants, with ant(6)-Ia, ant(9)-Ia, aph(3’)-IIIa, sat4, aadD1, and aac(6’)-Ie/aph(2’’)-Ia occurring in 14–22% of isolates worldwide. Temporal analysis revealed significant declines in several major determinants, most notably ant(9)-Ia (–2.22 percentage points per year, p < 0.001), whereas apmA exhibited a non-significant decreasing trend in animal isolates. Host structuring was marked: human clinical isolates concentrated common determinants, while animal and environmental isolates harbored rare alleles (apmA, spw, str, spd). Geographic mapping confirmed near-universal distribution of common genes but focal restriction of rare ones. Publicly available phenotypic data indicated strong activity of amikacin, whereas gentamicin showed a distinct resistant subpopulation that closely corresponded with AME gene carriage. Genotype–phenotype analyses demonstrated strong concordance, with gene-rich complements predicting resistant MIC strata and absence of determinants predicting susceptibility. Analysis across different gene classes revealed frequent co-occurrence of aminoglycoside resistance genes with determinants from other classes, such as mecA, blaZ, and MLS_B, embedding them within multidrug-resistant (MDR) genomic contexts. Over 25 years, the prevalence of aminoglycoside resistance-associated genes in S. aureus has declined for several common determinants, while rare veterinary-linked alleles are emerging in animal isolates. Strong genotype–phenotype concordance supports genomic prediction for gentamicin and amikacin, where MIC data are available, although phenotypic confirmation remains essential. The frequent co-occurrence of aminoglycoside resistance genes with other antimicrobial resistance determinants indicates their integration within co-occurrence patterns of MDR genes, defined here as clusters of co-occurring resistance genes often carried on shared mobile genetic elements. These patterns highlight the need for integrated One Health surveillance combining clinical, veterinary, and environmental monitoring with plasmid-context resolution to anticipate emerging threats.
Amr A. El-Sehrawy, S. Jasim, Haneen Fadhil Jasim et al.· BMC Microbiology· 0 citations
BACKGROUND
Antimicrobial resistance (AMR) in Helicobacter pylori is increasingly compromising eradication therapies worldwide. Despite growing concern, comprehensive global genomic analyses integrating resistance determinants, geographic distribution, and evolutionary patterns remain limited.
METHODS
A total of 6876 high-quality H. pylori genomes collected from 85 countries between 1900 and 2024 were analyzed. Resistance determinants were identified using AMRFinderPlus, followed by lineage profiling, geographic mapping, temporal trend analysis, and resistome characterization. The distribution of virulence-associated genes and resistance gene presence patterns was also evaluated.
RESULTS
Twenty-two AMR determinants were identified, predominantly chromosomal mutations. The most prevalent mutation was pbp1a S543R, associated with amoxicillin resistance, detected in 24.03% (1652/6876) of genomes across 63 countries since 1983. Fluoroquinolone resistance-associated gyrA N87K demonstrated a marked temporal increase, reaching approximately 50% prevalence by 2023. Additional gyrA and pbp1a variants were widely distributed globally. Acquired resistance genes, including blaTEM,aph(3')-IIIa, and catA1, were rare and primarily confined to sequence type 181. Among 2877 resistant isolates, 103 distinct resistance profiles were observed, with single-mutation patterns predominating. Geographic analysis revealed pbp1a S543R prevalence exceeding 40% in multiple Asian and African countries, while gyrA N87K exceeded 30% in parts of Asia and South America. The resistome exhibited an open structure, whereas 134 virulence-associated genes remained highly conserved.
CONCLUSIONS
This large-scale global genomic study demonstrates the extensive dissemination and ongoing evolution of AMR in H. pylori, particularly against amoxicillin and fluoroquinolones. The findings indicate that empirical treatment strategies based on these agents are becoming increasingly unsustainable worldwide. Implementation of susceptibility-guided therapy, rapid molecular diagnostics, and international genomic surveillance programs is urgently required to preserve eradication efficacy and limit further resistance expansion.
L. B. Alhusseini, Ali R. Laftah, F. N. Jaafar et al.· Infection, Genetics and Evol...· 0 citations
Background Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen causing severe hospital-acquired infections, especially in immunocompromised patients. The absence of an effective vaccine and rising antibiotic resistance underscore the need for novel interventions. This study employed an integrated reverse vaccinology and computational analyses to identify new immunogenic targets, design a multi-epitope vaccine (MEV), and propose potential drug targets. Methods A comprehensive immunoinformatics pipeline was employed to assess antigenicity, allergenicity, human similarity, and physicochemical properties of S. maltophilia proteins. Both B- and T-cell epitopes were screened; however, only the top B-cell epitopes were selected for MEV construction, given the extracellular nature of S. maltophilia. MEV–TLR interactions were analyzed through molecular docking and dynamics simulations. In parallel, cytoplasmic proteins were screened via a subtractive genomics approach to identify essential, non-human homologous, and non-microbiome-similar proteins, which were further evaluated for druggability and interaction networks to propose novel therapeutic targets. Results From a total of 4111 proteins, seven potential immunogenic targets were identified: GspD (WP_108270537.1), FhuE (WP_049451370.1), fimbrial protein (WP_012479122.1), TonB-dependent receptor (WP_169448402.1), TolC family protein (WP_108270106.1), autotransporter beta-barrel OMP (WP_169448945.1), and a hypothetical protein (WP_005407892.1). Subsequently, an MEV was designed using five immunogenic epitopes derived from four of these targets: WP_005407892.1 (ADQDSSNM), WP_049451370.1 (SGKAEQ and GEESKTPS), WP_108270537.1 (GVTSTQSDSERT), and WP_169448945.1 (RELGGDRNE). Molecular docking and molecular dynamics simulations demonstrated strong, stable, and feasible interactions between the MEV and TLR-2 and TLR-4 receptors. Moreover, nine novel drug targets were predicted for S. maltophilia, providing new therapeutic insights. Conclusion The designed MEV and identified immunogenic targets represent promising vaccine candidates against S. maltophilia. Further in vitro and in vivo studies are essential to confirm their safety, immunogenicity, and protective efficacy. Additionally, subtractive genomics analysis revealed nine novel, non-homologous drug targets, offering safer and more specific therapeutic avenues.
Safoura Moradkasani, N. Noori Goodarzi, M. Beig et al.· Journal of Genetic Engineeri...· 1 citation
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